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United States Patent |
5,347,217
|
Leach
,   et al.
|
September 13, 1994
|
Magnetic resonance spectroscopy and imaging
Abstract
In magnetic resonance spectroscopy or imaging, e.g. n.m.r. or e.s.r., a
method of localizing the region of a sample from which a resonance signal
is obtained by modulating the component M.sub.z of magnetization in the
B.sub.o direction according to position in the sample. This is achieved by
flipping the spins away from the B.sub.o direction, applying a gradient
magnetic field so that they lose or gain phase according to their
position, refocussing the effects of any resonance offsets including
chemical shifts and subsequently returning them to the B.sub.o direction
whereupon M.sub.z depends on the phase lost or gained and thus the
position. This may be repeated, possibly with different gradient fields or
different phase pulses, to further localize the region before a resonance
signal is finally detected. The contribution to the resonance signal
varies with M.sub.z and so is localized to regions of greater M.sub.z.
Inventors:
|
Leach; Martin O. (Wallington, GB);
Sharp; Jonathan C. (Leicester, GB)
|
Assignee:
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British Technology Group Limited (London, GB)
|
Appl. No.:
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966158 |
Filed:
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March 5, 1993 |
PCT Filed:
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July 25, 1991
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PCT NO:
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PCT/GB91/01247
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371 Date:
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March 5, 1993
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102(e) Date:
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March 5, 1993
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PCT PUB.NO.:
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WO92/02828 |
PCT PUB. Date:
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February 20, 1992 |
Foreign Application Priority Data
| Aug 02, 1990[GB] | 9016989.7 |
Current U.S. Class: |
324/309; 324/307 |
Intern'l Class: |
G01R 033/00 |
Field of Search: |
324/309,307,300
|
References Cited
U.S. Patent Documents
4509015 | Apr., 1985 | Ordidge et al. | 324/309.
|
4535290 | Aug., 1985 | Post et al. | 324/309.
|
4766380 | Aug., 1988 | Den Boef et al. | 324/309.
|
4891595 | Jan., 1990 | Granot | 324/309.
|
4947119 | Aug., 1990 | Ugurbil et al. | 324/307.
|
5049820 | Sep., 1991 | Briand et al. | 324/309.
|
5248942 | Sep., 1993 | Ratzel et al. | 324/309.
|
Foreign Patent Documents |
0209374 | Jan., 1987 | EP.
| |
2105853A | Mar., 1983 | GB.
| |
2122753A | Jan., 1984 | GB.
| |
2225640A | Jun., 1990 | GB.
| |
Other References
Magnetic Resonance in Medicine, vol. 12, No. 3, Dec. 1989, Duluth, USA-pp.
291-305.
Proceedings Of The National Academy of Sciences of USA, vol. 79, Jun. 1982,
Washington, USA-pp. 3523-3526.
Journal of Magnetic Resonance, vol. 68, 1968, Duluth, USA-pp.367-372.
|
Primary Examiner: Tokar; Michael J.
Assistant Examiner: Mah; Raymond Y.
Attorney, Agent or Firm: Harness, Dickey & Pierce
Claims
We claim:
1. A method of preparing the magnetization in a sample for magnetic
resonance comprising:
applying to the sample a first e.m. preparation pulse to flip the spins in
the sample away from the B.sub.o direction,
then applying a phase-encoding gradient magnetic field pulse of
predetermined magnitude and duration to the sample to give a positional
variation of phase in one direction in the sample,
and subsequently applying second e.m. preparation pulse to the sample to
return the spins to the B.sub.o direction, the phase variation encoded
during the application of the phase-encoding gradient magnetic field pulse
resulting in a predetermined spatial variation in magnetization along the
B.sub.o axis to enable a resonance signal to be then obtained from a
predetermined localized region in a single acquistition.
2. A method according to claim 1, wherein the e.m. preparation pulses are
non-selective.
3. A method according to claim 1, further comprising the steps of applying
one or more further episodes of e.m. preparation pulses and phase-encoding
magnetic field gradients without intermediate read-out of the resonance
signal whereby the localized region is more closely defined, said episodes
being followed by a single acquistion to obtain a resonance signal.
4. A method according to claim 3, wherein at least one of the direction and
magnitude of the phase-encoding gradient differs between repeat episodes
to further localize the region of the sample from which a resonance signal
will be obtained.
5. A method according to claim 1, further comprising the step of applying a
re-focussing e.m. pulse to the sample.
6. A method according to claim 5, wherein the re-focussing pulse is spaced
equally between the e.m. preparation pulses which respectively flip the
spins away from and return the spins to the B.sub.o field direction.
7. A method according to claim 1, wherein a gradient magnetic field is
applied after return of the spins to the B.sub.o direction to dephase any
remaining transverse components of spin.
8. A method according to claim 1, wherein the phase of the e.m. preparation
pulses is selected according to the localization required.
9. A method according to claim 1, wherein the amplitude of the preparation
pulses is selected so that the phase encoding gradient modulates the
magnetization component M.sub.z in the range .vertline.M.sub.o .vertline.
to zero.
Description
This invention relates to magnetic resonance spectroscopy and imaging and
in particular to the localization of signals from a sample.
Nuclear magnetic resonance spectroscopy and imaging and electron spin
resonance spectroscopy and imaging are widely-used techniques in medical
investigations and with both techniques localization of the "field of
view" to the particular volume of interest is important. A well-known
localization technique is the selection of a slice of spins through the
sample by applying a gradient magnetic field B.sub.o (thus making the
resonant frequency a function of position in the sample) during the same
period as a frequency-selective e.m. pulse is applied (Garroway, A. M.,
Grannell, P. K. and Mansfield, P., J. Phys.1C.7, L457 (1974)). However,
the slice position is dependent on chemical shift (influence of the atomic
and molecular electrons on the magnetic field experienced by the nucleus)
and also other resonant offset effects and so for samples including
species with varying chemical shifts (e.g. water and fat), the accuracy of
the localization is reduced (the region of water contributing to the
signal will be shifted slightly compared to the region of fat contributing
to the signal).
Similar problems arise in electron spin resonance techniques (sometimes
referred to as electron paramagnetic resonance) where although the
resonant frequency is of the order of 1000 times higher, the signal may be
spread over a wide spectral range.
Both n.m.r. and e.s.r. use electromagnetic excitation pulses to cause
resonance of the respective magnetic dipoles and as is known for n.m.r.
the excitation pulses are of radio frequency.
Phase encoding techniques are used to define position in imaging (see Kumar
A, et al, 1975 NMR Fourier zeugmatography J. Magn. Reson. 18 69-83 and
Edelstein W. A., et al 1980, Spin-warp NMR imaging and applications to
human whole-body imaging, Phys. Med. Biol. 25 751-6) and a simplified
example of a pulse sequence used in this technique is shown in FIG. 1 of
the accompanying drawings. As can be seen, localization to a slice
orthogonal to the z-direction is achieved by applying a gradient in the
z-direction, marked G.sub.z, and a 90.degree. e.m. pulse to flip spins in
a slice into the y-z plane. Localization in the x direction is obtained by
sampling the e.m. FID signal emitted from the sample during application of
a gradient in the x-direction, marked G.sub.x. Localization in the
y-direction is achieved by phase-encoding using the G.sub.y gradient
applied for a set time without any measurement e.m. pulse. During the
application of this gradient the phase of the rotation in the x-y plane of
the nuclear spins changes by an amount depending on the magnetic field
which they experience. Spins in a part of the sample with higher magnetic
field tend to gain phase, spins in a part of the sample with a lower
magnetic field tend to lose phase. The amount of gain or lag depends on
the magnitude of field and time for which it is applied and the gain or
lag is, of course, relative to the other spins in the sample. Thus after
application of G.sub.y the phase of the spin will be a function of the
position in the sample. By repeating the entire process with different
magnitude gradients, usually 256 times, and summing and performing a
Fourier transform on the result it is possible to obtain localized
information in the form of an image. The effects of chemical shift are
lost in the phase-encoding direction because the signal depends only on
the relative phase introduced between the spins in the repetitions, and
the chemical shift is the same each time.
It is possible to use phase-encoding to localize In the x-direction as
well, but 256.times.256 repetitions would be necessary and so the time
taken to perform the scans might be several hours, which is clearly
inappropriate for anything other than samples which can be kept perfectly
still.
For spectroscopy the number of repetitions in each direction can be reduced
to 8 or 16 and this allows Fourier phase-encoding to be used as the
localization technique for all three directions but the resolution is
reduced (see: Proc. Natl. Acad. Sci. 79, 3523 (1982) by T. R. Brown, B. M.
Kincaid and K. Ugurbil). Further, to retrieve the spatial information a
3-D Fourier transformation is required.
The present invention provides a technique where phase-preparation can be
used to define a localized region or regions of the sample from which
signals will be obtained, thus avoiding chemical shift or other spin
resonant frequency effects, but avoiding the multiplicity of read-outs
(i.e. the combination of a pulse interrogating the z-axis followed by data
acquisition) required by the prior art methods using phase-encoding. This
will be referred to as a Phase Encoded Selection Technique or PEST. Thus
the invention uses phase-preparation to define the region of the sample
from which read-out is to be obtained, rather than a frequency selective
e.m. pulse combined with a gradient field. The spatial selectivity can be
adjusted by repeating the preparation period a number of times prior to a
single read-out.
According to one aspect the present invention provides a method of
preparing the magnetization in a sample for magnetic resonance comprising
phase-preparing the spins. In the sample to define a localized region or
regions of the sample from which a resonance signal can be detected. The
region or regions may be more sharply defined by performing a plurality of
phase-preparation steps before read-out of the resonance signal.
According to another aspect the present invention provides a method of
phase-preparation of the magnetization in a sample for magnetic resonance
comprising applying a series of e.m. preparation pulses to the sample in
the absence of a slice-selective gradient magnetic field and also applying
a phase- encoding gradient magnetic field to the sample to define a
localized region or regions of the sample from which signal may be
obtained in a single acquisition.
According to another aspect the present invention involves applying a
phase-preparation gradient magnetic field to a sample to define a
localized region or regions of the sample from which resonance signal is
to be obtained and subsequently applying one or more further
phase-encoding magnetic field gradients each with preparation e.m. pulses
but without intermediate read-out of the resonance signal, thereby to more
closely define the localized region or regions.
In any of the above aspects the method may include preliminary application
of a preparation e.m. pulse before each phase-encoding gradient, for
instance a pulse to flip the spins into the plane orthogonal to the
B.sub.o direction and may also include a refocussing pulse after the
phase-preparation gradient. This may be followed by an e.m. pulse to
return the spins to the B.sub.o -axis. The e.m. pulses may have phases
selected to act on groups of spins having particular phases. Preferably
the refocussing pulse occurs at the centre of the interval between the
e.m. pulse flipping the spins out of the B.sub.o -axis and the e.m. pulse
returning them. This timing alleviates chemical shift and other spin
resonant frequency offset effects on the results. This sequence may be
followed by application of a spoiling gradient magnetic field to dephase
any remaining transverse components of the nuclear spins.
The preparation steps may include the application of more than one
phase-preparing gradient magnetic field (each in the absence of a
simultaneous e.m. pulse), for example a positive gradient for a time
before the refocussing pulse and a negative gradient after (which add to
the effect of the first because of the reversal the axis of spin induced
by the refocussing pulse). Alternatively the gradient field may be
smoothly varied throughout the time between the two "flip" e.m. pulses as
long as it is low or zero during the refocussing pulse.
Following the above preparation steps an e.m. read pulse is applied and the
FID resonance signal detected.
Several PEST sequences each with read-out but different preparation
episodes (e.g. phase cycling) may be performed and the results (acquired
signals) combined to improve the performance (e.g. the localization or
tolerance to instrumental deficiencies).
Further, PEST sequences may be combined with other techniques, e.g. imaging
or a localized spectroscopy sequence, to produce a desired type of scan.
The invention also provides for each of the above methods, corresponding
apparatus for magnetic preparation of magnetic resonance samples having
means operative to carry out the steps thereof.
The invention may be applied to both imaging and spectroscopy and may be
implemented by suitable reprogramming of an existing magnetic resonance
controller or by use of a dedicated hard-wired controller.
The invention will be further described by way of non-limitative example
with reference to the accompanying drawings, in which:
FIG. 1 shows a prior art imaging technique;
FIG. 2 shows a pulse sequence according to one embodiment of the present
invention;
FIG. 3 shows the result of a scan obtained following use of a preparation
sequence according to FIG. 2;
FIGS. 4-6 show the localization which can be achieved using different
repeats of the preparation sequence of the present invention; and
FIG. 7 shows schematically a sequence of e.m. pulses used in a further
embodiment of the invention.
A basic PEST pulse sequence is illustrated in FIG. 2. It consists of a
first e.m. pulse 90x, with a phase of 0.degree. relative to the x-axis in
the rotating frame of reference, which flips the spins into the x-y plane,
followed by a phase-encoding gradient G.sub.e. The direction of the
phase-encoding gradient is chosen according to the localization required.
This is followed at a time T after the 90x pulse by a refocussing pulse
180y with phase +90.degree. relative to the x-axis which refocuses or
re-phases the spins (which tend to gradually dephase due to chemical shift
and B.sub.o inhomogeneities) by flipping the spins through 180.degree..
It should be noted that phase differences of multiples of 2.pi. are
indistinguishable and so if the phase preparation gradient is steep enough
there may be several disconnected regions whose phases differ by 2.pi. but
which will contribute signal to the result.
After a further time T the spins are returned to the z-direction by a
90.phi.-x e.m. pulse (i.e. with phase .phi. relative to the x-axis) such
that as the spin phase progressively diverges from .phi., the component of
magnetization returned to the z-axis, M.sub.z, decreases. It is this
variation in M.sub.z which is subsequently read. Then any remaining
transverse components of spin are de-phased by a spoiling gradient pulse
G.sub.s. This sequence, with modified pulses or gradients as desired is
repeated, if desired, to sharpen or more closely define the region or
regions which will contribute the resonance signal. Then a 90.degree. x
e.m. pulse is applied and the resulting FID resonance signal detected.
Unlike earlier phase-encoding techniques no Fourier transform is required
to decode the spatial information as the signal acquired is localized to
that region or those regions with maximum M.sub.z.
It will be noted that no gradients are applied during any of the e.m.
pulses. Thus the spins in the whole sample are treated. The effect of the
phase-encoding is to, modulate Mz sinusoidally with position, thus by
repeated applications the desired response, localized to a region, may be
built-up. FIGS. 4-6 shows how the profile can be sharper for increasing
numbers of repeats. After the desired number of preparation sequences the
resonance signal is obtained by for example application of a 90.degree.
e.m. pulse and the F.I.D. is detected. FIG. 3 shows an n.m.r. scan
obtained with 1 preparation episode followed by an imaging sequence to
read the signal. This shows an image of the selection achieved with the
technique, where a phantom with oil at the top and water towards the
bottom of the image was used and the technique was used to select vertical
stripes. There was no chemical shift evident due to the selection the
slices, although the chemical shift artifact apparent the images is due to
the readout gradient used in displaying the images.
Other preparation sequences are also possible and may improve the
localization achieved with fewer repeats. For instance, a 45x - 180y -
45x-.phi. sequence as shown in FIG. 7 results in a sinusoidal modulation
of M.sub.z over the range from -M.sub.o to zero, rather than +M.sub.o to
-M.sub.o as obtained above. This is in effect a - (sine squared) function
which provides superior localization compared to a sine modulariot and a
single 45 - 180 - 45 sequence achieves the same effect as two 90 - 180 -
90 steps thus reducing by a factor of two the number of steps required and
facilitating practical implementation. A number of variants in terms of
phase and amplitude of this sequence are as follows:
______________________________________
45x 180y 45x-phi
135x 180y 135x-phi
225x 180y 225x-phi
135x 180y 45x-phi
______________________________________
The 45 - 180 - 45 sequence, and related sequences, result in a -(sine
squared) H.sub.z response, whereas the 135 - 180 - 45 sequence, and
related sequences, result in a +(sine squared) response, which may be less
prone to the effects of T1 relaxation. The 45 - 180 - 45 sequences however
may be less affected by errors in flip angles, being partially sell
compensating for these errors.
The effect of the 90x - 180y - 90.phi.-x pulse sequence can be calculated
as follows:
Neglecting relaxation and using exact 90.degree. and 180.degree. pulses,
the effect of N preparation episodes on a spin system at equilibrium
(magnetization M.sub.o) is given exactly by:
##EQU1##
where r is a position vector, .phi. is a phase angle as defined in the
pulse sequence, and k(p)=.gamma..delta.G.sub.E (p)dt. Equations [2]& [3]
give the conditions for maxima (M.sub.z (r.sub.1)=M.sub.o) and zero
(M.sub.z (r.sub.2)=0) responses respectively (m integer):
.phi.(p)+k(p).multidot.r.sub.1 =m.pi. (for all p) [2]
.phi.(p)+k(p).multidot.r.sub.2 =.pi./2+m.pi. (for at least 1 p) [3]
One solution of Eqn [2] resulting in a periodic one dimensional M.sub.z (r)
response (N even; period=.pi./k(N); one maximum at r.sub.1 =0), is given
by:
##EQU2##
For this solution the profile of the selected slice is positive everywhere
and tends to a sinc.sup.2 function with FWHM .ltoreq..pi./2k(1), becoming
slightly narrower as N increases. Side lobes are small for N =10 episodes,
but can be minimized if required by the use of extra episodes. Slice
position is determined by .phi.(p), as given by Eqn.[2].
The repeat episodes need not include an identical phase-preparation
gradient--it can be switched in magnitude. and/or direction in order to
localize differently. Similarly the return pulse can have a different
phase. Further, the gradients can be in different directions so that the
regions selected intersect and signal is obtained primarily from the
intersection of the regions.
Thus, PEST is a single-shot B.sub.o gradient localization method which
eliminates chemical shift localization errors. The technique finds
particular application in n.m.r. for nuclei with a wide chemical shift
range. RF power requirements are intermediate between CSI and frequency
selective methods. Phase-cycled multiple volume schemes using several
acquisitions are possible, due to the periodic nature of the excitation-
NMR localization images can be used to select the volume, which may then
be positioned under software control.
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